PB1856: MUTATION STATUS AND ALLELE BURDEN OF FLT3-ITD IN ACUTE MYELOID LEUKEMIA
Authors: Asiyat Radzhabova, Ekaterina Motyko, Lubov Polushkina, Marina Zenina, Anastasiya Kuzyaeva, Irina Martynkevich, Sergey Voloshin
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Currently, a fundamental role in the prognosis of acute myeloid leukemia (AML) is associated with chromosomal aberrations and genetic abnormalities, which allow not only correctly stratifying patients into risk groups, thereby optimizing the intensity of cytostatic chemotherapy (CT) and timely planning of allogeneic hematopoietic stem cell transplantation (allo-HSCT), but also allow to use the entire arsenal of target drugs. The most common mutations among AML patients are FLT3 (ITD and TKD), which are considered to be potential predictors of poor disease prognosis. Aims: To assess the effect of the mutational status of the FLT3 gene and the impact of the FLT3-ITD allele burden (AB) value on the course of AML. Methods: A retrospective analysis of the FLT3 gene mutation status effect on the clinical features and course of the disease was carried out with involvement of 199 AML patients. The dynamics of the FLT3-ITD gene mutation AB value against the background of standard chemotherapy and allo-HSCT programs, as well as the impact of this dynamics on survival rates, were analyzed in 91 AML patients. Results: In the study group of the AML patients, the frequency of FLT3 gene mutations accounted for 30.5% of all considered cases (FLT3-ITD - 24% (48/199), FLT3-TKD - 5.5% (11/199), a co-occurrence of FLT3-ITD and FLT3-TKD - 1.0% (2/199)), the rest - 69.5% (138/199) of patients had no mutations in the FLT3 gene. Two groups were identified in accordance with the FLT3-ITD gene mutation AB value: low AB (<0.5) - n=50 (55%) group and high AB (≥0.5) - n=41 (45%) group. The presence of mutations in the FLT3 gene was characterized by a higher level of peripheral blood leukocytes (p<0.001). At the same time, patients with high AB in the FLT3-ITD gene, compared with patients with low AB, demonstrated high leukocytosis (p<0.001) and bone marrow blastosis (p=0.04). The percentage decrease in the FLT3-ITD AB associated with administration of chemotherapy significantly correlated with relapse-free survival and OS (r=0.45; p<0.01 and r=0.46; p<0.01, respectively). A significant decrease in AB after CT compared with pre-treatment data was found only in patients with complete remission of the disease (p<0.01). Mutations in the NPM1 gene were detected significantly more often in the FLT3-ITD group of patients – 37 (32.4%) out of 114 patients (p=0.0001). However, the presence of mutation in the NPM1 gene did not improve OS in patients with high FLT3-ITD AB. The results of overall survival depending on the mutational status are presented in Figures 1 and 2. The use of allo-HSCT as a therapeutic option significantly improves OS: in the group with high FLT3-ITD after allo-HSCT+ (n=15) treatment the follow-up median was not reached, while in the group that did not get allo-HSCT- (n=10) it was 2.5 months (p=0.00008). Summary/Conclusion: AML patients with mutations in the FLT3 gene remain one of the complex categories of patients requiring timely prescription of targeted drugs and allo-HSCT, which allows achieving improved survival rates.Keywords: FLT3, Acute myeloid leukemia